Sapkal Priyanka R, Tatiya Anilkumar U, Firke Sandip D, Redasani Vivek K, Gurav Shailendra S, Ayyanar Muniappan, Jamkhande Prasad G, Surana Sanjay J, Mutha Rakesh E, Kalaskar Mohan G
R. C. Patel Institute of Pharmaceutical Education & Research, Shirpur, Maharashtra 425405, India.
Yashoda Technical Campus, Faculty of Pharmacy, Satara, Maharashtra 412 802, India.
Heliyon. 2023 Apr 29;9(5):e15952. doi: 10.1016/j.heliyon.2023.e15952. eCollection 2023 May.
This study aimed to assess the phytochemical composition, antioxidant, cytotoxicity, and anti-inflammatory activities of the methanolic extract of Ailanthus excelsa (Simaroubaceae) stem bark and its fractions. Quantitative phytochemical analysis revealed that methanolic extract and all fractions contained a high level of flavonoids (20.40-22.91 mg/g QE), phenolics (1.72-7.41 mg/g GAE), saponins (33.28-51.87 mg/g DE), and alkaloids (0.21-0.33 mg/g AE). The antioxidant potential was evaluated using a range of assays, i.e., DPPH•, ABTS radical scavenging ability, and total antioxidant capacity. The chloroform and ethyl acetate fractions showed stronger antioxidant activity than the methanol extract. In vitro cytotoxic activity was investigated in three human tumor cell lines (A-549, MCF7 and HepG2) using the SRB assay. In addition, the anti-inflammatory effect was assessed by carrageenan-induced paw edema in rats. The chloroform fraction showed a more pronounced effect by effectively controlling the growth with the lowest GI50 and TGI concentrations. The human lung cancer cell line (A-549) was found to be more sensitive to the chloroform fraction. Furthermore, the chloroform fraction exhibited significant anti-inflammatory activity at a dose of 200 mg/kg in the latter phase of inflammation. Besides, methanol extract and ethyl acetate fraction revealed a significant cytotoxic and anti-inflammatory effects. The chloroform fraction of stem bark showed a strong anti-inflammatory effect in experimental animals and significant COX-2 inhibitory potential in the experiments. GC-MS analysis of chloroform fraction identified the phytochemicals like caftaric acid, 3,4-dihydroxy phenylacetic acid, arachidonic acid, cinnamic acid, 3-hydroxyphenylvaleric acid, caffeic acid, hexadeconoic acid, and oleanolic acid. The results suggest that identified compounds have better affinity towards the selected targets, viz. the BAX protein (PDB ID: 1F16), p53-binding protein Mdm-2 (PDB ID: 1YCR), and topoisomerase II (PDB ID: 1QZR). Amongst all, caftaric acid exhibited the best binding affinity for all three targets. Thus, it can be concluded that caftaric acid in combination with other phenolic compounds, might be responsible for the studied activity. Additional and studies are required to establish their exact molecular mechanisms and consider them as lead molecules in developing of valuable drugs for treating oxidative stress-induced disorders, cancers, and inflammations.
本研究旨在评估臭椿(苦木科)茎皮甲醇提取物及其馏分的植物化学成分、抗氧化、细胞毒性和抗炎活性。定量植物化学分析表明,甲醇提取物及其所有馏分均含有高水平的黄酮类化合物(20.40 - 22.91毫克/克槲皮素当量)、酚类化合物(1.72 - 7.41毫克/克没食子酸当量)、皂苷(33.28 - 51.87毫克/克地奥皂苷元当量)和生物碱(0.21 - 0.33毫克/克阿托品当量)。使用一系列测定方法评估抗氧化潜力,即DPPH•、ABTS自由基清除能力和总抗氧化能力。氯仿和乙酸乙酯馏分显示出比甲醇提取物更强的抗氧化活性。使用SRB测定法在三种人类肿瘤细胞系(A - 549、MCF7和HepG2)中研究体外细胞毒性活性。此外,通过角叉菜胶诱导的大鼠足肿胀评估抗炎作用。氯仿馏分通过以最低的GI50和TGI浓度有效控制生长显示出更显著的效果。发现人肺癌细胞系(A - 549)对氯仿馏分更敏感。此外,氯仿馏分在炎症后期以200毫克/千克的剂量表现出显著的抗炎活性。此外,甲醇提取物和乙酸乙酯馏分显示出显著的细胞毒性和抗炎作用。茎皮的氯仿馏分在实验动物中显示出强烈的抗炎作用,并且在实验中具有显著的COX - 2抑制潜力。氯仿馏分的GC - MS分析鉴定出了如咖啡酰酒石酸、3,4 - 二羟基苯乙酸、花生四烯酸、肉桂酸、3 - 羟基苯戊酸、咖啡酸、十六烷酸和齐墩果酸等植物化学物质。结果表明,鉴定出的化合物对选定的靶点,即BAX蛋白(PDB ID:1F16)、p53结合蛋白Mdm - 2(PDB ID:1YCR)和拓扑异构酶II(PDB ID:1QZR)具有更好的亲和力。其中,咖啡酰酒石酸对所有三个靶点表现出最佳的结合亲和力。因此,可以得出结论,咖啡酰酒石酸与其他酚类化合物结合,可能是所研究活性的原因。需要进一步的研究来确定它们的确切分子机制,并将它们视为开发用于治疗氧化应激诱导的疾病、癌症和炎症的有价值药物的先导分子。